Therapeutic Bispecific T-Cell Engager Antibody Targeting the Transferrin Receptor
Therapeutic Bispecific T-Cell Engager Antibody Targeting the Transferrin Receptor
复制标题
靶向转铁蛋白受体的治疗性双特异性 T 细胞接合抗体
DOI：
10.3389/fimmu.2019.01396
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发表时间：
2019-06-21
影响因子：
7.3
通讯作者：
Lei, Ping
中科院分区：
文献类型：
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作者：
Fu, Mingpeng;He, Qi;Lei, Ping
双特异性T细胞结合抗体(BITE)已被探索为一种招募细胞溶解T细胞来杀伤肿瘤细胞的方法。转铁蛋白受体(TFR)在快速增殖的肿瘤细胞表面高度表达。因此，它在T细胞重定向治疗方面具有巨大的潜力。在本研究中，我们开发了一种针对TFR和CD3的BIT(TFR-BIT)，并研究了其对TFR阳性癌症的治疗作用。TFR-BITE通过激活T细胞，释放细胞因子，进而促进T细胞的增殖，诱导多种TFR阳性肿瘤细胞的选择性裂解，而TFR阴性的肿瘤细胞不受影响。在HepG2皮下移植模型中，低浓度的TFR-BITE抑制肿瘤生长。总之，这些结果表明，TFR-BITE可以选择性地耗尽TFR阳性的HepG2细胞；因此，它代表了一种治疗肝细胞癌的新的免疫治疗方法。
Bispecific T-cell engager antibodies (BiTE) have been explored as a means to recruit cytolytic T cells to kill tumor cells. The transferrin receptor (TfR) is highly expressed on the surface of rapidly proliferating tumor cells. Therefore, it holds great potential in T cell redirecting therapies. In this research, we developed a BiTE targeting TfR and CD3 (TfR-BiTE) and studied its therapeutic impact on TfR-positive cancer. TfR-BiTE had the ability to induce the selective lysis of various TfR-positive cancer cells through the activation of T cells, the release of cytokines, and then the coming proliferation of T cells, whereas TfR-negative cells were not affected. In a subcutaneous HepG2 xenograft model, low concentrations of TfR-BiTE inhibited tumor growth. Overall, these results reveal that TfR-BiTE can selectively deplete TfR-positive HepG2 cells; hence, it represents a novel immunotherapeutic approach for the treatment of hepatocellular carcinoma.